In order to understand better the pathogenesis of phenylketonuria as well as normal brain function, we plan to investigate further origins of the disturbance in myelin elaboration in infant animals with high phenylalanine levels, specifically as it relates to inhibition of glial cell metabolism. In addition we will attempt to contrast effects of the lipid disturbances and deficient biogenic amine synthesis on the electrophysiological parameters of the cortically evoked potential (CER) in the developing brain of hyperphenylalaninemic animals. Our studies of disturbed amino acid transport and glycoprotein metabolism will be continued. Having found the CER a useful means of documenting a functional response to dietary treatment in chronic, severely retarded PKU patients, we will extend our investigations to include PKU and its variants with and without treatment in younger patients. The therapeutic aim is to evaluate not only the effect of phenylalanine restriction but to define also a group in which alternative or adjunctive treatments might be useful.